噻托溴銨在COPD大鼠氣道炎癥中的作用_《中國呼吸與危重監護雜志》

作者：

何牡丹 , 榮令 ,  周新

上海交通大學第一附屬醫院呼吸科（上海 200080）;

關鍵詞：

慢性阻塞性肺疾病　托溴銨氣道炎癥氣道阻力白細胞介素8 白三烯B4

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目的探討噻托溴銨對COPD氣道炎癥和氣道阻力的影響。方法 30 只大鼠隨機分為3 組, 每組10 只。正常對照組: 正常飼養28 d; 模型組: 第1 d和第14 d 氣管內滴入脂多糖200 μg,每日煙熏( 第1 d 和第14 d 除外) , 共28 d; 治療組: 與模型組相同的方法建立COPD模型, 并于每日煙熏前30 min 霧化吸入噻托溴銨( 生理鹽水溶解, 0. 12 mmol /L, 10 min) 共28 d。大鼠處死前行肺功能測定; 取左肺BALF 進行細胞分類計數; 肺組織HE 染色行病理學評價; ELISA法測定BALF 及血清IL-8 和白三烯B4 ( LTB4 ) 濃度。結果 ①模型組大鼠的氣道阻力顯著高于正常對照組, 順應性明顯降低( P lt;0. 01) ; 治療組大鼠氣道阻力較模型組明顯降低( P lt; 0. 01) , 順應性明顯增加( P lt;0. 05) 。②模型組氣道炎癥加重, 且出現明顯肺氣腫; 治療組也出現了炎癥和肺氣腫, 但程度較輕。③ 模型組BALF 中細胞總數、中性粒細胞比例明顯升高; 治療組細胞總數、中性粒細胞比例較模型組明顯降低。④模型組血清及BALF 中IL-8 和LTB4 濃度均較正常對照組明顯升高( P lt;0. 01) , 治療組與模型組比較IL-8 和LTB4 水平顯著降低( P lt;0. 01) 。結論噻托溴銨可以減輕COPD大鼠的氣道炎癥, 延緩肺功能惡化, 這一作用可能是通過抑制炎癥介質的釋放來實現的。

引用本文： 何牡丹,榮令,周新. 噻托溴銨在COPD大鼠氣道炎癥中的作用. 中國呼吸與危重監護雜志, 2009, 09(3): 212-215. doi: 復制

1.	Sato E, Koyama S, Okubo Y, et al. Acetylcholine stimulates alveolar macrophages to release inflammatory cell chemotactic activity. Am J Physiol, 1998 , 274 : L970 -L979.
2.	Tashkin DP, Celli B, Senn S, et al. A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease. N Engl J Med, 2008 , 359 :1543-1554.
3.	王長征. 藥物治療能改變慢性阻塞性肺疾病患者肺功能的下降速率嗎? 中國呼吸與危重監護雜志, 2009, 8: 1-2.
4.	Saito Y, Azuma A, Morimoto T, et al. Tiotropium ameliorates symptoms in patients with chronic airway mucus hypersecretion which is resistant to Macrolide therapy. Intern Med,2008, 47: 585-591.
5.	張弛, 林如平, 劉洪, 等. 魚腥草注射液對慢性阻塞性肺疾病患者炎癥細胞因子與肺功能影響. 中國中醫藥科技, 2006, 13: 294-295.
6.	Profita M, Bonanno A, Siena L, et al. Acetylcholine mediates the release of IL-8 in human bronchial cells by a NFκB/ ERKdependent mechanism. Eur J Pharmacol, 2008, 582: 145-153.
7.	Bühling F, Lieder N, Kuhlmann UC, et al Tiotropium suppresses acetylcholine-induced release of chemotactic mediators in vitro.Respir Med, 2007, 101: 2386-2394.
8.	宋一平, 崔德健, 茅培英, 等. 慢性阻塞性肺疾病大鼠模型氣道重塑及生長因子的研究. 中華結核和呼吸雜志, 2001, 24: 283-287.
9.	Gosens R, Bos IS, Zaagsma J, et al. Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling. Am J Respir Crit Care Med, 2005, 171: 1096-1102.
10.	張永, 程德云, 王慧, 等. 慢性阻塞性肺疾病大鼠肺內白細胞介素-8 和腫瘤壞死因子-α與氣道炎癥的關系研究. 中國呼吸與危重監護雜志, 2003, 2: 553-558.
11.	謝靜. 重癥急性呼吸綜合征患者血漿細胞因子水平的動態改變. 中華內科雜志, 2003, 42: 643-645.
12.	Keatings VM, Collins PD, Scott DM, etal. Differences ininterleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med, 1996, 153: 530-534.
13.	Crooks SW, Bayley DL, Hill SL, et al. Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis: the role of leukotriene B4. Eur Respir J, 2000, 15: 274-280.
14.	Hill AT, Bayley D, Stockley RA. The interrelationship of sputum inflammatory markers in patients with chronic bronchitis. Am J Respir Crit Care Med, 1999, 160: 893-898.
15.	Turner CR, Breslow R, Conklyn MJ, et al. In vitro and in vivo effects of leukotrien B4 antagonism in a primate model of asthma. J Clin Invest, 1996, 97: 381-387.
16.	Profita M, Giorgi RD, Sala A, et al. Muscarinic receptors, leukotriene B4 production and neutrophilic inflammation in COPD patients.Allergy, 2005, 60: 1361-1369.
17.	Jiménez E, Montiel M. Activation of MAP kinase by muscarinic cholinergic receptors induces cell proliferation and protein synthesis in human breast cancer cells. J Cell Physiol, 2005, 204: 678-686.。.

1. Sato E, Koyama S, Okubo Y, et al. Acetylcholine stimulates alveolar macrophages to release inflammatory cell chemotactic activity. Am J Physiol, 1998 , 274 : L970 -L979.
2. Tashkin DP, Celli B, Senn S, et al. A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease. N Engl J Med, 2008 , 359 :1543-1554.
3. 王長征. 藥物治療能改變慢性阻塞性肺疾病患者肺功能的下降速率嗎? 中國呼吸與危重監護雜志, 2009, 8: 1-2.
4. Saito Y, Azuma A, Morimoto T, et al. Tiotropium ameliorates symptoms in patients with chronic airway mucus hypersecretion which is resistant to Macrolide therapy. Intern Med,2008, 47: 585-591.
5. 張弛, 林如平, 劉洪, 等. 魚腥草注射液對慢性阻塞性肺疾病患者炎癥細胞因子與肺功能影響. 中國中醫藥科技, 2006, 13: 294-295.
6. Profita M, Bonanno A, Siena L, et al. Acetylcholine mediates the release of IL-8 in human bronchial cells by a NFκB/ ERKdependent mechanism. Eur J Pharmacol, 2008, 582: 145-153.
7. Bühling F, Lieder N, Kuhlmann UC, et al Tiotropium suppresses acetylcholine-induced release of chemotactic mediators in vitro.Respir Med, 2007, 101: 2386-2394.
8. 宋一平, 崔德健, 茅培英, 等. 慢性阻塞性肺疾病大鼠模型氣道重塑及生長因子的研究. 中華結核和呼吸雜志, 2001, 24: 283-287.
9. Gosens R, Bos IS, Zaagsma J, et al. Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling. Am J Respir Crit Care Med, 2005, 171: 1096-1102.
10. 張永, 程德云, 王慧, 等. 慢性阻塞性肺疾病大鼠肺內白細胞介素-8 和腫瘤壞死因子-α與氣道炎癥的關系研究. 中國呼吸與危重監護雜志, 2003, 2: 553-558.
11. 謝靜. 重癥急性呼吸綜合征患者血漿細胞因子水平的動態改變. 中華內科雜志, 2003, 42: 643-645.
12. Keatings VM, Collins PD, Scott DM, etal. Differences ininterleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med, 1996, 153: 530-534.
13. Crooks SW, Bayley DL, Hill SL, et al. Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis: the role of leukotriene B4. Eur Respir J, 2000, 15: 274-280.
14. Hill AT, Bayley D, Stockley RA. The interrelationship of sputum inflammatory markers in patients with chronic bronchitis. Am J Respir Crit Care Med, 1999, 160: 893-898.
15. Turner CR, Breslow R, Conklyn MJ, et al. In vitro and in vivo effects of leukotrien B4 antagonism in a primate model of asthma. J Clin Invest, 1996, 97: 381-387.
16. Profita M, Giorgi RD, Sala A, et al. Muscarinic receptors, leukotriene B4 production and neutrophilic inflammation in COPD patients.Allergy, 2005, 60: 1361-1369.
17. Jiménez E, Montiel M. Activation of MAP kinase by muscarinic cholinergic receptors induces cell proliferation and protein synthesis in human breast cancer cells. J Cell Physiol, 2005, 204: 678-686.。.

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